Robert Clancy

Biosketch / Results /

Robert Clancy

Associate Professor, Department of Medicine
Medicine

Contact Info

Address
301 East 17th Street
New York, NY 10003

212/263-0751
Robert.Clancy@nyumc.org

Research Summary

The interaction between the extracellular matrix and cells affects a wide spectrum of cellular processes including migration, growth, death, capacity to degrade matrix, capacity to synthesize matrix, differentiation, and cell attachment. In human neutrophils, we study signalling by beta1 integrin receptors which contribute to cell attachment and migration. Additionally, we study the effect of nitric oxide, an inflammatory mediator, on the signalling pathways. Neutrophils help destroy foreign invaders at tissue sites but first must reversibly undergo cell attachment through the endothelium and matrix. We hypothesize that nitric oxide modulates matrix-cell interaction by the reversible inhibition of neutrophil attachment to fibronectin (ligand for beta1 integrin)-coated surfaces. We recently showed that nitric oxide inhibits adherence associated with a stimulation of actin-ADP ribosylation. In bovine chondrocytes, we study signalling by beta1 integrin receptors which contribute to the capacity to degrade matrix and differentiation. We hypothesize that nitric oxide, a mediator of arthritis, inhibits chondrocyte adherence and cell capacity to contribute to matrix synthesis and breakdown. Recently, we studied signalling by beta1 integrins in chondrocytes by measuring protein accumulation to contact sites in chondrocytes exposed to fibronectin-coated and albumin-coated beads. Chondrocytes exposed to albumin-coated beads failed to generate a response, but cytoskeletal and signalling molecules accumulated to fibronectin-coated and albumin-coated beads which include polymerized actin, focal adhesion kinase, and the accumulation of tyrosine phosphorylated proteins (see Figure). Prior treatment of chondrocytes with catabolic cytokines (which stimulate nitric oxide synthesis) prevent the response. Collectively, our results suggest that nitric oxide induced a persistently altered chondrocyte phenotype (chondrocytes incapable of signalling via beta 1 integrins) which might be reversed or prevented by using nitric oxide antagonists. A persistently altered state in chondrocytes would greatly change the ability of such chondrocytes to mature and perhaps result in the changes seen in arthritis.

Research Interests

Molecular Mechanism of beta1 Integrin Signal Transduction

Novel Role of Liver X Receptor Alpha (LXR alpha) in the Attenuation of TLR Signalling: Implications in Congenital Heart Block.
Bagchi, Susmita; Halushka, Mark; Clancy, Robert M; Buyon, Jill P
2015-01-29; 2326-5205,Arthritis & rheumatology - id: 1443992, year: 2014

Letter to the Editor in response to the article "Preventing congenital neonatal heart block in offspring of mothers with anti-SSA/Ro and SSB/La antibodies: A review of published literature and registered clinical trials." by Gleicher N, Elkayam U, Autoimmun Rev. 2013 Sep;12(11):1039-45
Costedoat-Chalumeau, Nathalie; Izmirly, Peter; Wahren-Herlenius, Marie; Silverman, Earl; Brucato, Antonio; Boutjdir, Mohamed; Khamashta, Munther; Llanos, Carolina; Pisoni, Cecilia N; Friedman, Deborah M; Clancy, Robert; Phoon, Colin K L; Saxena, Amit; Buyon, Jill P
2013-11-18; 1568-9972,Autoimmunity reviews - id: 628742, year: 2014 Letter

Modulation of Natural IgM-Autoantibodies to Oxidative Stress-Related Neo-Epitopes on Apoptotic Cells in Newborns of Mothers with Anti-Ro Autoimmunity
Groenwall, Caroline; Clancy, Robert M; Getu, Lelise; Siegel, Don L; Reed, Joanne; Buyon, Jill P; Silverman, Gregg J
2015-01-29; 2326-5205,Arthritis & rheumatology - id: 1444002, year: 2014

Levels of IgG Autoantibodies to Oxidation-Associated MDA Neo-Determinants Are a Biomarker for Systemic Inflammation and Disease Activity in SLE and RA
Groenwall, Caroline; Getu, Lelise; Greenberg, Jeffrey D; Clancy, Robert M; Silverman, Gregg J
2015-01-29; 2326-5205,Arthritis & rheumatology - id: 1443952, year: 2014

Relation of carotid plaque with natural IgM antibodies in patients with systemic lupus erythematosus
Gronwall, Caroline; Reynolds, Harmony; Kim, June K; Buyon, Jill; Goldberg, Judith D; Clancy, Robert M; Silverman, Gregg J
2014-05-08; 1521-6616,Clinical immunology - id: 960172, year: 2014 JOURNAL ARTICLE